TY - JOUR
T1 - Fructose consumption reduces hippocampal synaptic plasticity underlying cognitive performance
AU - Cisternas, Pedro
AU - Salazar, Paulina
AU - Serrano, Felipe G.
AU - Montecinos-Oliva, Carla
AU - Arredondo, Sebastián B.
AU - Varela-Nallar, Lorena
AU - Barja, Salesa
AU - Vio, Carlos P.
AU - Gomez-Pinilla, Fernando
AU - Inestrosa, Nibaldo C.
N1 - Publisher Copyright:
© 2015.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of metabolic disorders comprising diabetes and obesity. The impact of MetS on the brain is becoming to be a concern, however, the poor understanding of mechanisms involved has limited the development of therapeutic strategies. We induced a MetS-like condition by exposing mice to fructose feeding for 7. weeks. There was a dramatic deterioration in the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD). Mice exposed to fructose showed a reduction in the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation likely associated with a deficiency in plasma membrane excitability. Consistent with an overall hippocampal dysfunction, there was a subsequent decrease in hippocampal dependent learning and memory performance, i.e., spatial learning and episodic memory. Most of the pathological sequel of MetS in the brain was reversed three month after discontinue fructose feeding. These results are novel to show that MetS triggers a cascade of molecular events, which disrupt hippocampal functional plasticity, and specific aspects of learning and memory function. The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders.
AB - Metabolic syndrome (MetS) is a global epidemic, which involves a spectrum of metabolic disorders comprising diabetes and obesity. The impact of MetS on the brain is becoming to be a concern, however, the poor understanding of mechanisms involved has limited the development of therapeutic strategies. We induced a MetS-like condition by exposing mice to fructose feeding for 7. weeks. There was a dramatic deterioration in the capacity of the hippocampus to sustain synaptic plasticity in the forms of long-term potentiation (LTP) and long-term depression (LTD). Mice exposed to fructose showed a reduction in the number of contact zones and the size of postsynaptic densities (PSDs) in the hippocampus, as well as a decrease in hippocampal neurogenesis. There was an increase in lipid peroxidation likely associated with a deficiency in plasma membrane excitability. Consistent with an overall hippocampal dysfunction, there was a subsequent decrease in hippocampal dependent learning and memory performance, i.e., spatial learning and episodic memory. Most of the pathological sequel of MetS in the brain was reversed three month after discontinue fructose feeding. These results are novel to show that MetS triggers a cascade of molecular events, which disrupt hippocampal functional plasticity, and specific aspects of learning and memory function. The overall information raises concerns about the risk imposed by excessive fructose consumption on the pathology of neurological disorders.
KW - Diabetes
KW - Fructose
KW - Metabolic syndrome
KW - Neuronal dysfunction
UR - http://www.scopus.com/inward/record.url?scp=84940781575&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2015.08.016
DO - 10.1016/j.bbadis.2015.08.016
M3 - Article
AN - SCOPUS:84940781575
SN - 0925-4439
VL - 1852
SP - 2379
EP - 2390
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 11
ER -